A faster CO2 fractional scanner system mode for skin rejuvenation. A clinical study

Abstract Background The market requires ever‐faster techniques, in particular for pre‐rejuvenation condition. Aim The purpose of this study was to assess if a fractional CO2 scanner modality (called moveo) results in a faster full‐face rejuvenation treatment in comparison to the standard mode, currently existing in the scanner system. Materials and Methods A total of 12 female patients affected by fine lines participated in a split‐face clinical investigation and underwent to two sessions with a fractional CO2 laser system equipped with an existing and a faster dedicated scanner units. Pain was assessed using VAS. Three‐dimensional clinical photographs were captured before, immediately after, 3 days, 14 days after the first treatment and immediately after the second treatment and 1 months after the last one. The uniformity and aesthetic coverage of treatments were assessed using dermatoscopy. Global aesthetic improvement scale (GAIS) was used. The time taken to treat the two sides of the face and all possible side effects were monitored. Results Following only two treatment session with both scanner modes, the patient's skin texture improved significantly, with fine lines reduction. There is no statistically significant difference in perceived pain between patients. The GAIS score showed satisfactory results following both modalities. The time parameters indicated that with the faster scanner mode the full‐face treatment time was reduced by 30% compared to the standard one. No adverse effects were observed. Conclusions The moveo modality provide faster treatment and a better final dermal aesthetic outcome than the standard procedure while maintaining the same safety profile.


INTRODUCTION
In Europe, the aging process ranks as the fourth most frequent natural skin phenomena.The first obvious indication of facial aging is typically the development of periocular wrinkles and fine lines.
There are many different factors that contribute to skin aging, such as structural, physiological, and biochemical alterations. 1 Loss of skin tonicity in all dermal districts can be attributed to extrinsic causes including smoking, nutrition, and general lifestyle choices, as skin aging is a continuous process.[4] Due to the loss of volume and segmentation of the facial compartments, the cumulative effects of these age-related changes can result in significant changes in the appearance of the face.6][7] When combined, these modifications may have an effect on an individual's confidence, self-worth, and body image.
The mechanism of wrinkles formation appears to involve qualitative and quantitative changes on the dermis and extracellular matrix components, 8 free radicals cellular damages and impaired dermal blood vessels 9 an increase of the static contraction of the facial muscles due to aging and stress. 10Facial wrinkles are divided into superficial and deep.Among these, the superficial wrinkles are caused mainly by facial movements (also called expression lines) and are visible on the forehead, glabella, lateral eyes (crow's feet) and mouth.[16] However, fillers can cause less allergic reactions and have a lower immunogenicity, but they need to be immobile and take longer to resorb in order to be suitable for use in biomedical field.
Furthermore, several papers from the scientific literature report adverse effects from filler 17 such as allergic reaction, 18 inflammatory nodule formation 19 infection, purpura 20 vision loss 21 and restricted use in patients with compromised immune systems. 22pical therapies, such sunscreen, retinoids, and antioxidants, are simple, low-risk interventions that unquestionably aid in the reduction and prevention of wrinkles.However, since lasers can access the skin's dermal layer and start rejuvenating changes at the dermal cellular layer, they are an ideal alternative for reducing small wrinkles given the previously outlined pathophysiology of skin aging and rhytid development.
The fully ablative carbon dioxide (CO 2 ) laser was created and first used in 1968.It was the first widely accepted method of enhancing photoaging. 23e effectiveness of skin rejuvenation following fully ablative laser treatment may still be unrivaled, but this aggressive procedure comes with a high price in terms of ex-tended social withdrawal and the possibility of challenging-to-treat long-term side effects, such as dyspigmentation, infection, scarring, and prolonged erythema. 24e most recent laser literature suggests fractional photothermolysis as a potentially better efficacy-to-risk ratio alternative to fully ablative technology for the treatment of fine wrinkling of photoaging on the face, chest, neck, and hands. 25aditional ablative lasers have been transformed into fractional devices that use fractional photo thermolysis, which limits thermal injury to a specific pattern of small columns of dermis and epidermis known as microthermal zones (MTZs).This reduces the possibility of side effects.Only a small portion of the skin has been thermally ablated, allowing the surrounding tissue to remain intact to promote neocollagenesis and fast re-epithelialization. 26 An ablative CO 2 fractional resurfacing device with several MTZs that may be customized in terms of depth and density and can penetrate the stratum corneum, epidermis, and dermis was shown by Hantash and colleagues in 2007. 27They also demonstrated immunohistochemistry using forearm skin from in vivo models, and they found that sustained collagen remodelling persisted for at least 3 months following treatment.
Compared with traditional lasers, the fractional ablative CO 2 laser can effectively im-prove skin regeneration, with shorter downtime and significantly fewer side effect.
The fractionated CO 2 has the potential to have a bigger and longer effect on skin collagen remodelling and synthesis since it induces a higher degree of injury than previous models.
Histologic and ultrastructural findings point to a wound repair process for fractional laser healing in addition to increased deposition of new collagen, similar to other laser modalities. 28 addition to inducing an enhanced undulating rete (papillary) ridge pattern-which is typically absent or diminished in aging skintreatment with fractional CO 2 also in-creases the formation of mucin in the papillary and superficial reticular dermis 29 Reilly and colleagues 30 demonstrated statistically significant alterations in the gene clarified in fully ablative CO 2 laser resurfacing, and they suggested comparable molecular mechanisms of action for both fractional and totally ablative CO 2 laser resurfacing.
Additional research has demonstrated that the CO 2 laser's ablative fractional photo-thermolysis (AFP) caused a decrease in the thickness of the subepidermal low-echogenic band (SLEB) and an increase in skin thickness.The area of the papillary dermis containing solar elastosis is known as the SLEB.
In a pilot investigation with CO 2 AFP, Tierney and colleagues 31 reported on improvements in textural and pigmentary characteristics in photoaged skin.In particular, they saw mean score improvements of 61%, 54%, and 52%, respectively, for dyschromias, skin laxity, and rhytides.The average improvement in the overall appearance was sixty percent.Additional research has verified the safety and efficacy of CO 2 ablative fractional resurfacing procedures in treating periorbital and perioral rhytidosis.
Periorbital wrinkles have been successfully treated using fractional ablative laser. 32cent studies demonstrated also the efficacy of the combination of fractional laser and platelet-rich plasma therapy 33 to accelerate the face rejuvenation healing process. 34actional ablative lasers offer a lower recovery time and erythema onset than standard ablative lasers, resulting in a greater safety profile. 26These advantages, along with the corresponding decrease in scarring and pigmentation impairment, have led to the growing acceptance of fractional laser therapies. 35Most patients desiring this treatment are younger and want improvement without any down time.
Indeed, nowadays, the market requires ever-faster techniques, in particular for pre-rejuvenation condition or mild rejuvenation, that result in the patient's ideal post-treatment condition without any aesthetic discomfort, such as bronzing of the skin, scratches, or superficial flaking. 36sed on these scientific findings, a fractional CO 2 laser scanner system with a novel treatment modality (moveo mode) that supports the standard modality currently existing in the scanner and can expedite treatment session times while expanding the scanning area, has been developed.
The purpose of the current investigation was to assess if the moveo mode results in a faster full-face treatment in comparison to the standard one with a consequent greater satisfaction for patients and operators.
In order to evaluate these clinical settings, a total of 12 patients were treated with SmartXide Tetra PRO (DEKA M.E.L.A Srl, Florence, Italy) equipped with this dedicated scanner system (DOT PRO scanner, DEKA M.E.L.A, Florence, Italy).Treated areas were the cheek, chin and forehead.For each patient a full split-face treatment was performed with no overlapping of the two CO 2 laser scanner modalities (moveo mode was conducted on the left side of the face, while standard mode was performed on the right side).

Patient's population and study device protocols
A total of two sessions at 45 days intervals, applying the same parameters of energy for DOT and spacing on both facial sides, were performed.For both scanner modes the following parameters were applied: power of 5-15 W, Spacing 700 µm, scan mode SmartTrack and HP pulse.In the case of skin rejuvenation treatments, the clinical endpoint is mild facial reddening related to a perception of warmth that should re-solve within a few minutes.
Immediately after the procedure, wet cold gauzes were applied to the treated surface, kept moist, and cool using air cooler).

F I G U R E 1 Graphical representation of fractional standard mode.
The scanner can be moved in any direction but without overlapping the scan areas.

Description of CO 2 laser scanner system
DOT PRO scanner can be used in two modalities: standard or moveo modes.In standard mode, the handpiece must be perpendicular to the skin surface and remain in that position until the system has completed the whole scanning area of 20 × 20 mm.After that the handpiece must be moved in such a way that there is no overlap be-tween several scanning areas (Figure 1).This modality covers all types of treatments, from pre-rejuvenation (preventative anti-ageing skincare treatments) to major rejuvenations treatments (such as deep wrinkles and acne scars).
In moveo mode, the scanner performs a single line of DOTs up to 20 mm long, so it will be necessary to move perpendicular to the axis of the scan line as described in the Figure 2.This mode was designed for mild rejuvenation treatments (e.g., fine wrinkles treatments).This scanner can be equipped with a contact sensor to ensure greater safety during treatment and a particular spacer with rounded end-pieces in order to facilitate the sliding of the scanner over the skin during moveo treatment.

Clinical assessment
All patients gave a pain quantification for both treatment modalities The uniformity of the dermatoscopic DOTs pattern was evaluated with a score from 0 to 4. Similarly, the aesthetic coverage of the DOTs on the treated area was also evaluated with a score from 0 to 4.
In addition, in order to monitor skin recovery, the days necessary for the expulsion of the fibrin plugs was monitored.
The aesthetic clinical outcomes of patients were also evaluated by the global aesthetic improvement scale (GAIS): 4, excellent improvement 3, good improvement; 2, moderate improved; 1, mild improvement; and 0, no change.
Furthermore, to assess the efficiency of the two treatments, the time taken to treat the two sides of the face was monitored.
All possible side effects were monitored.
Finally, patients were asked which of the two treatment modalities they would or would not recommend to others.

RESULTS
All the 12 patients have completed the clinical evaluation.In this clinical test, after only two treatment session with moveo and standard modes, the patient's skin texture improved significantly, with fine lines reduction as confirmed by the photographic documentation and dermatoscopy analysis (Figure 3-7).
Dermatoscopy analysis revealed that the mean score for the uniformity of the DOTs pattern was 3.4 ± 0.5 for moveo mode and 3.7 ± 0.5 for standard mode.
In addition, the mean score calculated for the aesthetic coverage of the DOTs on treated area was 3.6 ± 0.5 for moveo mode and 3.5 ± 0.5 for the standard one.These differences are not statistically significant (p > 0.05).
According to the VAS pain scale, the mean pain level was 2.9 ± 1.0 following moveo treatment modality and 3.1 ± 0.9 following standard treatment mode.The pain scale values resulted very similar, since there is no statistically significant difference in perceived pain between patients.The GAIS score showed satisfactory results following both modalities; for moveo facial side, excellent improvement was achieved by four patients, good improvement was achieved by four patients and moderate improved was achieved by four patients.The total mean GAIS score was 3.0 ± 0.9.
For standard facial side, excellent improvement was achieved by five patients, good improvement was achieved by three patients and moderate improved was achieved by four patients.The total mean GAIS score was 3.1 ± 0.9.The difference between the two mean GAIS scores were not statistically significant (p > 0.05).
The mean patient's treatment time was 67.9 ± 10.1 s for moveo mode and 99.8 ± 7.6 s for standard mode.These time parameters were statistically significant (p < 0.05) and they indicated that with the moveo mode the full-face treatment time was reduced by 30% compared to the standard mode resulting in a faster and more satisfying treatment mode for patients and operators.
The average days required for expulsion of fibrin plugs observed was 7.1 ± 0.9 days following moveo mode treatment and 7.2 ± 1.0 following standard mode treatment (p > 0.05).
No infections, scars or any other adverse effects were observed.

DISCUSSION
Nowadays, more than ever, younger generations appreciate the necessity of beginning preventative anti-aging skin care procedures earlier than any previous generation.Pre-rejuvenation is an active rather than reactive approach to anti-aging skincare.Instead of introducing medical-grade skin care into their daily routine after the appearance of fine lines, wrinkles, and sun damage, younger generations are beginning to include these products in their 20s and 30s to maintain a more youthful appearance.
One of the main benefits of pre-skin rejuvenation is that it is much easier to slow the signs of aging than to correct skin that has already lost collagen and developed signs of sun damage.This allows those starting preventative skin care to avoid having to use more aggressive treatments later in life.Furthermore, public demand for faster heal- Ken Arndt in 2013 coined the term prejuvenation, "to prevent the loss of youth", to put forth the concept that if one successfully prejuvenated early in life, then it would not be necessary in later years to seek rejuvenation. 38is concept is gaining more awareness with particular acceptance among younger patients.
Ageing results from multiple factors, including elastic fibre degeneration from chronic sun exposure and cumulative mechanical stress from facial muscle movements.

F I G U R E 5
Female patient affected by photoaging signs on her face, treated with moveo mode (left side) and with standard mode (right side), immediately after (A), after 3 days (B), after 14 days (C) and at 1 month follow up (D).The corresponding dermatoscopic analysis considering a precise skin area was carried out for moveo mode (left black circle) immediately after (E), after 3 days (F), after 14 days (G) and at 1 month follow up (H), and for standard mode (right black circle), immediately after (I), after 3 days (J), after 14 days (K) and at 1 month follow up (L).
A number of mechanisms, starting in the late 20s to mid-30s, contribute to facial volume loss associated with aging.These processes include soft tissue atrophy, muscle and bone resorption, and downward displacement of structural fat pads.Although there are many advantages to premature aging, it's important to explain to patients that it can only slow down, not completely reverse, the aging process.
Non-invasive cosmetic procedures like chemical peels, microdermabrasion, laser skin rejuvenation, dermal fillers, and skincare regimens to preserve a youthful glow are some common protocols or approaches.[41] Among these, light and laser technologies have been proven to effectively reduce photodamage by promoting the production of collagen type I and III and elevating the expression of heat shock protein. 42,43 a retrospective analysis of 15 patients who received routine broadband light treatments at least once a year for 5-11 years, blinded examiners estimated their posttreatment age to be an average of 2 years younger than their actual age at study initiation, despite the fact that they aged a median of 9 years. 42Light-based interventions can impact and perhaps prevent skin aging at the histologic, molecular and clinical levels.
The aging skin changes in numerous ways.The face lines represent a reflection of sun exposure and age.Treating facial fine wrinkles, or atrophic rhytids, is a significant task for cosmetic specialists.These tiny wrinkles are caused by alterations in the skin's microrelief, which result in parallel, finely wrinkled lines that vanish when the skin is stretched. 44creases in the extracellular matrix's glycosaminoglycans, oxytalan elastin fibres, and cutaneous collagen VII bundles are the underlying pathophysiology of fine line generation.Photoaging is primarily caused by a class of enzymes known as matrix metalloproteinases, which speed up natural aging by breaking down extracellular matrix, collagen, and elastin in the dermis.A photoaging process called solar elastosis results in thick wrinkles as a by-product of the haphazard deposition of bulky, disorganized collagen, which leaves deep, permanent wrinkles in its wake. 45thorough medical history and a targeted physical examination of the skin in natural light are the first steps in the clinical evaluation of these facial wrinkles.
Dermal thinning is the fundamental cause of fine lines, commonly referred to as atrophic rhytids.Numerous molecular processes have been linked to the deterioration of dermal architecture and strength.
The loss of collagen and elastin in the dermis is the cause of dermal thinning.Practitioners can have a better understanding of the pre- Female patient affected by photoaging signs on her face, treated with moveo mode (left side) and with standard mode (right side), immediately after (A), after 3 days (B), after 14 days (C) and at 1 month follow up (D).The corresponding dermatoscopic analysis considering a precise skin area was carried out for moveo mode (left black circle) immediately after (E), after 3 days (F), after 14 days (G) and at 1 month follow up (H), and for standard mode (right black circle), immediately after (I), after 3 days (J), after 14 days (K) and at 1 month follow up (L).
vention and treatment of fine lines by reading the histology of the involvement of dermal atrophy in the formation of fine wrinkles.The creation of wrinkles is not significantly influenced by the epidermis, despite the superficial appearance of fine lines and wrinkles.The fine atrophic rhytids on the face are actually the result of deeper molecular alterations in the underlying dermis.Thus, the stigmata associated with older skin can be effectively treated using laser rejuvenation therapies that penetrate the dermis and cause neocollagenesis and dermal remodeling. 46As previously discussed in the Introduction section the most recent laser literature suggests fractional photothermolysis as a potentially better efficacy-to-risk ratio alternative to fully ablative technology for the treatment of fine wrinkling of photoaging on the face, chest, neck, and hands. 25ecifically fractional CO 2 laser represent a successful treatment for fin lines reduction. 47rthermore, the development of scanned CO 2 lasers to check the depth of ablation was found to be important for its safety and efficacy profiles.
In the current study the development of faster and different scanner modalities allowed us to evaluate the performance of an innovative CO 2 fractional laser in the treatment of fine lines.Indeed, our findings showed that the photographic clinical evaluation indicated that both treatment methods lead to a positive change of skin texture and a visible fine lines reduction in all patients examined.
As represented by photographic assessment and GAIS score analysis at 1 month follow-up after the last treatment, all the subjects examined showed a visible improvement of skin texture with a reduction of fine lines without discomfort following both treatment modalities.
The average pain levels evaluated by VAS following the two treatment modalities demonstrated that neither scanning modes was painful or caused the patient discomfort.
Using both scanner settings, the representative clinical images reported in this split face clinical evaluation better highlighted marked facial aesthetic improvement, with positive change of skin texture and a visible fine lines reduction.Indeed, the majority of patients achieved an excellent/good improvement according to GAIS scale results.
Nevertheless, the moveo mode has the additional advantage to be faster than the standard mode as the scanner can be moved perpendicular to the axis of the scan line without having to wait that the scanner complete the entire scanning area.Furthermore, the moveo mode decreasing the probability of overlapping zones forming between the scan areas (as happens in the standard mode) thus also decreasing the risk of adverse effects and resulting in a better dermal aesthetic result without marked scan areas on the skin.

F I G U R E 7
Female patient affected by photoaging signs on her face, treated with moveo mode (left side) and with standard mode (right side), immediately after (A), after 3 days (B), after 14 days (C) and at 1 month follow up (D).The corresponding dermatoscopic analysis considering a precise skin area was carried out for moveo mode (left black circle) immediately after (E), after 3 days (F), after 14 days (G) and at 1 month follow up (H), and for standard mode (right black circle), immediately after (I), after 3 days (J), after 14 days (K) and at 1 month follow up (L).
In addition, with the use of moveo mode, treatment time was reduced by 30% compared to the standard one, resulting in a faster and more patient's satisfying treatment technique.Indeed, as a consequence, our findings showed that the majority of treated subject (58 % of patients) prefer and recommend the moveo treatment modality.
Finally, dermatoscopic images and quantitative analysis showed that similar results for DOT uniformity/distribution and calculated scores for DOT aesthetic coverage on the treated area were obtained with both scanning modalities.These results suggested that both scanner modalities are efficient to cover and to treat the interest area with the significant advantages achieved by the use of moveo mode as previously mentioned in this paragraph.
Furthermore, the use of Dermoscopy analysis corroborates the results of this study, since there are no guidelines for assessing skin photoaging; for this reason, Dermoscopy represents a noninvasive detection technique that may be beneficial for evaluating photoaging. 48,49e Hu 50 and Isik 51 dermoscopy scores are currently used methods for evaluating photoaging.Dermoscopy can accurately visualize and improve pigmentation and wrinkles, decreasing the impact of subjectivity and significant correlations between dermoscopic scores and clinical scales were found. 52In addition, Dermoscopy acts as a link between clinical and histological testing.It reveals the microscopic structure of the epidermis to the superficial layer of the dermis in an unseen and dynamic manner. 53

Study limitation
Our study's limitation is represented by a restricted patient sample.
Our long-term goal is to increase patient numbers, as well as to extend the follow-up period.

CONCLUSIONS
The post-treatment results presented in this clinical study demonstrated that good improvement in fine lines and skin texture can be achieved with the use of both CO 2 laser scanner modalities.However, the moveo mode has demonstrated the ability to provide faster treatment, higher patient satisfaction and a better final dermal aesthetic outcome than the standard procedure while maintaining the same safety profile.

ACKNOWLEDGMENT
This research received no external funding.

A
total of 12 female patients affected by fine lines and skin tone unevenness, were enrolled for this clinical study and they provided a written informed consent prior to participating.Patients' mean age was 48.3 (±16) years and the patients' phototypes ranged between II and III.Patient's exclusion criteria included: recent exfoliation treatment, lifting, previous skin disorders including keloids.Patients participated in a split-face clinical investigation, and they were treated with the SmartXide Tetra PRO (DEKA M.E.L.A Srl, Florence, Italy) equipped with a dedicated scanner unit (DOT PRO scanner).This scanner creates microthermal zones of ablation and coagulation (DOTs), separated from healthy tissue by a spacing parameter (spacing), and it deposits these DOTs with two modalities: standard or moveo mode.

F I G U R E 2
using the visual analog scale (VAS from 0, no pain to 10, worst pain possible).A photographic evaluation by doctor specialized in aesthetic medicine and with vast experience in dermo-aesthetic treatments was performed in order to assess the improvement of fine lines, skin tone, and overall appearance comparing the moveo and the standard mode.Three-dimensional (3D) clinical photographs of the face were captured at three angles (left, centre, and right) before treatments, immediately after, 3 days, 14 days after the first treatment and imme-Graphical representation of fractional moveo mode.The scanner can be moved perpendicular to the axis of the scan line.diatelyafter the second treatment and 1 months after the last one, using the 3D digital camera (Vectra H2, Canfield, USA) for a better and more objective evaluation of the patient in terms of vascularity and tissue texture.The change in the distribution of DOTS was assessed with a greater accuracy and also monitored for optimum end point and post-therapy assessment of the laser treatments, using dermatoscopy (or epiluminescence microscopy, (ELM)) (FotoFinder Systems GmbH 1000, Bad Birnbach, Germany) at the same following time points.

F I G U R E 3 F I G U R E 4
Frontal view of a female patient's face before (A) and immediately following moveo mode (left side) and standard mode (right side) treatments (B).Female patient affected by photoaging signs on her face, treated with standard mode (right side) and with moveo mode (left side).Clinical images were acquired before (A;G), immediately after (B;H), after 3 days (C;I), after 14 days (D;J), immediately after two treatment sessions (E;K) and at 1 month follow up (F;L).ing treatments with better natural state maintenance has increased, leading to a shift in skin rejuvenation techniques at public requests.It has long been recommended that sun protection slows the progression of age-related skin changes.In an effort to restore skin health, cosmeceuticals, neurotoxins, dermal fillers, and energy-based devices are now also utilized to lessen photodamage and delay cellular senescence.While reversing the signs of age receives the majority of therapeutic attention, in 2003 scientists started to reframe our concepts about preventing or delaying the signs of aging.37